当前位置: X-MOL 学术Cancer Lett. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors.
Cancer Letters ( IF 9.1 ) Pub Date : 2020-09-03 , DOI: 10.1016/j.canlet.2020.08.035
Lin Qi 1 , Mari Kogiso 1 , Yuchen Du 1 , Huiyuan Zhang 1 , Frank K Braun 1 , Yulun Huang 2 , Wan-Yee Teo 3 , Holly Lindsay 1 , Sibo Zhao 1 , Patricia Baxter 4 , Xiumei Zhao 1 , Litian Yu 1 , Zhigang Liu 5 , Xingding Zhang 6 , Jack Mf Su 4 , Adekunle Adesina 7 , Jianhua Yang 4 , Murali Chintagumpala 4 , Laszlo Perlaky 4 , Chris Tsz-Kwong Man 4 , Ching C Lau 8 , Xiao-Nan Li 1
Affiliation  

Brain tumor is the leading cause of cancer related death in children. Clinically relevant animals are critical for new therapy development. To address the potential impact of animal gender on tumorigenicity rate, xenograft growth and in vivo drug responses, we retrospectively analyzed 99 of our established patient derived orthotopic xenograft mouse models (orthotopic PDX or PDOX). From 27 patient tumors, 5 glioblastomas (GBMs), 11 medulloblastomas (MBs), 4 ependymomas (EPNs), 4 atypical teratoid/rhabdoid tumors (ATRTs) and 3 diffuse intrinsic pontine gliomas (DIPGs) that were directly implanted into matching locations in the brains of approximately equal numbers of male and female animals (n = 310) in age-matched (within 2-week age-difference) SCID mice, the tumor formation rate was 50.6 ± 21.5% in male and 52.7 ± 23.5% in female mice with animal survival times of 192.6 ± 31.7 days in male and 173.9 ± 34.5 days in female mice (P = 0.46) regardless of pathological diagnosis. Once established, PDOX tumors were serially subtransplanted for up to VII passage. Analysis of 1595 mice from 59 PDOX models (18 GBMs, 18 MBs, 5 ATRTs, 6 EPNs, 7 DIPGs and 5 PENTs) during passage II and VII revealed similar tumor take rates of the 6 different tumor types between male (85.4 ± 15.5%) and female mice (84.7 ± 15.2%) (P = 0.74), and animal survival times were 96.7 ± 23.3 days in male mice and 99.7 ± 20 days in female (P = 0.25). A total of 284 mice from 7 GBM, 2 MB, 1 ATRT, 1 EPN, 2 DIPG and 1 PNET were treated with a series of standard and investigational drugs/compounds. The overall survival times were 106.9 ± 25.7 days in male mice, and 110.9 ± 31.8 days in female mice (P = 0.41), similar results were observed when different types/models were analyzed separately. In conclusion, our data demonstrated that the gender of SCID mice did not have a major impact on animal model development nor drug response in mice, and SCID mice of both genders are appropriate for use.



中文翻译:

SCID 小鼠性别对儿童脑肿瘤原位 PDX 模型中致瘤性、异种移植物生长和药物反应的影响。

脑肿瘤是儿童癌症相关死亡的主要原因。临床相关动物对于新疗法的开发至关重要。解决动物性别对致瘤率、异种移植物生长和体内的潜在影响药物反应后,我们回顾性分析了 99 个我们建立的患者来源的原位异种移植小鼠模型(原位 PDX 或 PDOX)。27 例患者肿瘤中,5 例胶质母细胞瘤 (GBM)、11 例髓母细胞瘤 (MB)、4 例室管膜瘤 (EPN)、4 例非典型畸胎瘤样/横纹肌样瘤 (ATRT) 和 3 例弥漫性内源性脑桥神经胶质瘤 (DIPG) 被直接植入到匹配位置在年龄匹配(年龄差异在 2 周内)的 SCID 小鼠中,对大约相同数量的雄性和雌性动物 (n = 310) 的大脑进行研究,雄性小鼠的肿瘤形成率为 50.6 ± 21.5%,雌性小鼠为 52.7 ± 23.5%雄性小鼠的动物存活时间为 192.6 ± 31.7 天,雌性小鼠的存活时间为 173.9 ± 34.5 天(P = 0.46)无论病理诊断如何。一旦建立,PDOX肿瘤被连续亚移植直至第VII代。对第 II 代和第 VII 代中来自 59 个 PDOX 模型(18 GBM、18 MB、5 ATRT、6 EPN、7 DIPG 和 5 PENT)的 1595 只小鼠进行的分析显示,雄性之间 6 种不同肿瘤类型的肿瘤发生率相似(85.4 ± 15.5%) )和雌性小鼠(84.7 ± 15.2%)(P  = 0.74),雄性小鼠的动物存活时间为 96.7 ± 23.3 天,雌性小鼠为 99.7 ± 20 天(P  = 0.25)。来自 7 GBM、2 MB、1 ATRT、1 EPN、2 DIPG 和 1 PNET 的总共 284 只小鼠接受了一系列标准和研究药物/化合物的治疗。雄性小鼠的总生存时间为106.9±25.7天,雌性小鼠的总生存时间为110.9±31.8天(P = 0.41),当单独分析不同类型/模型时,观察到类似的结果。总之,我们的数据表明 SCID 小鼠的性别对动物模型的发育和小鼠的药物反应没有重大影响,并且两种性别的 SCID 小鼠都适合使用。

更新日期:2020-09-03
down
wechat
bug